Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit hepatologist.eu
Hepatorenal Syndrome 2018 - Boca Raton Regional...
Transcript of Hepatorenal Syndrome 2018 - Boca Raton Regional...
Hepatorenal Syndrome
2018
Warren Kupin, MD FACP
Professor of Medicine
Miami Transplant Institute
Katz Family Division of Nephrology and Hypertension
University of Miami Miller School of Medicine
Case Presentation
60 year male with Diabetes
Cirrhosis : NASH
Stable : well compensated
U.S. Prevalence
3.9 million with liver disease
633,000 cases of Cirrhosis
New cases of Cirrhosis / yr
30,000
Deaths / yr
20-40,000
10 yrs
(58% of all cases)
Ascites
Stable : well compensated
Portal HTN
1 -5 yrs
(20 – 40% of all cases)
Hepatorenal
Syndrome
crea
t
years
GF
R
years
60
Outline of Discussion Topics
Treatment of HRS Pathophysiology of HRS Definition of Hepatorenal Syndrome (HRS) Assessment of Kidney Function in patients with
Liver Disease
• What are the diagnostic criteria for Hepatorenal Syndrome (HRS) ?
• Does a patient with HRS have Acute Kidney Injury or Chronic Kidney
Disease or Both ?
• Or is it Fake News and there is no “True” kidney disease ?
• What is the pathophysiology behind the development of HRS ?
• What therapeutic options are available for HRS ?
• Does a patient with Cirrhosis and HRS need a Liver Transplant only or a
combined Liver and Kidney Transplant ?
• Will we finish this topic before noon ?
Importance of Accurate Assessment
of Renal Function in Liver Disease
Diagnosis / Treatment response
of HRS
Determine the need
for combined
liver / kidney
Transplantation
Calculate the
MELD score
Determine
drug dosing
Serum Creatinine
• Creatine
• Synthesized in the liver and stored in muscle
• Also ingested orally and localized to muscle
• Creatinine
• Cyclic anhydride of creatine (nonenzymatic)
• End product of muscle metabolism
• Renal excretion of creatinine
– GFR - filtration
– Tubular secretion
Origin of
Creatinine Oral Ingestion-Meat
(creatine)
Muscle
(Energy source-
Metabolized)
Hepatic Synthesis
(creatine)
50%
50%
Creatinine
Range of Creatinine Values
in the Population
0
10
20
30
40
50
60
< 0.7 0.7 - 0.8 0.9 - 1.0 1.1 - 1.2 1.3 - 1.4 1.5 - 1.6 1.7 - 1.8 1.9 - 2.0
Male Female
The normal creatinine level is
relative to muscle mass
Women < 1.2 mg/dl
Men < 1.5 mg/dl
(represents 2 SD above the mean)
0.95 1.15
1.13
0.49
0.44
0
0.2
0.4
0.6
0.8
1
1.2
Controls Liver disease no
portal HTN
Liver Disease
Portal HTN
Creatine Production in Patients with Cirrhosis
Gliedman et al. Ann Surg 174:892, 1971
50% decrease in creatine
production in liver disease
Lower Baseline Creatinine Levels than the
Normal Population
– Cirrhosis
• Minimal protein intake with severe malnutrition
• Impaired liver synthesis of creatine
– Pregnancy
• Volume expansion and an increase in GFR
– Extremes of age/nutrition – pediatric / elderly
– Baseline or “normal” creatinine in these conditions may be 0.4 - 0.6 mg/dl
– Patients can be in AKI or CKD in all these circumstances with serum creatinines of 1.1 mg/dl
Bilirubin Interference and Creatinine Measurement
Jaffe Reaction
Creatinine + picric acid Creatinine – picric acid
complex
Reaction is read at a specific wavelength (570)
Bilirubin absorbs light at 570 which leads to a spuriously
low serum creatinine
Usually noted with a bilirubin level > 25 mg/dl
Assessment of Renal Function in Cirrhosis:
Inaccuracy of the Serum Creatinine
Decreased Protein Intake
Decreased Muscle Mass
Decreased Hepatic Creatine Synthesis
Spuriously Low Creatinine Measurement with Hyperbilirubinemia
GFR and Cirrhosis
Arroyo V, J Hepatol 46:935, 2007
Stage 2 CKD
Stage 3 CKD
Stage 4 CKD
Stage 5 CKD
Normal
At serum Creatinine levels < 1.5 mg/dl : a significant proportion of patients with
cirrhosis will have GFRs < 60 cc/min : much greater than the general population
Cirrhosis
Kidney Function in Cirrhosis
Creatinine
Real and Spurious decrease in serum concentration
Renal Function “appears” better than it really is
GFR
True decline in GFR compared to the general
population
Majority of these patients will have serum creatinine
levels < 1.5 mg/dl
The CKD-EPI formula is not an accurate predictor of GFR and alternative formulas using cystatin C may be considered
Assessment of Renal Function in Cirrhosis:
Inaccuracy of the BUN
Decreased Protein Intake
Decreased hepatic synthesis
Reduced efficacy of the BUN/Cr ratio to detect pre-renal azotemia
Possible disproportionate increase in BUN in the setting of GI bleed
Hepatorenal Syndrome :
Diagnostic Criteria –
International Ascites Club 2015
• Cirrhosis or Acute Hepatic disease and Portal Hypertension
• Cr Increase of 0.3 mg/dl in 48 hrs or a 50% increase over 7 days
• Absence of nephrotoxic agents
• Absence of shock
• Absence of renal parenchymal disease
– Proteinuria < 500 mg/d
– No Hematuria
– Normal renal ultrasound (size/echogenicity)
• No improvement after 48 hours following
– Diuretic withdrawal
– volume expansion with
• Albumin 1 g/kg/day ( maximum 100 g)
Definition of AKI in the General Population
• Increase of the serum creatinine by 0.3 mg/dl
within 48 hours
OR
• Increase in serum creatinine by > 50%
(over 7 days)
OR
• Urine output < 0.5 ml/kg/hr for more than 6
hours
International Ascites Club 2015
Revised Definition of AKI
in Patients with Cirrhosis
• Increase of the serum creatinine by 0.3 mg/dl
within 48 hours
OR
• Increase in serum creatinine by > 50%
(over 7 days)
OR
• Urine output < 0.5 ml/kg/hr for more than 6
hours
Conditions Causing
Simultaneous Renal and Liver Failure
• Hepatorenal syndrome
• Acute tubular necrosis
• Volume depletion
• Circulatory
– CHF
– Shock
• Genetic: ADPKD
• Collagen vascular disease
• Infections
– Sepsis
– Leptospirosis
– Reye’s
syndrome
– Hepatitis A
– Hepatitis B
– Hepatitis C
Conditions Causing
Simultaneous Renal and Liver Failure
• Toxins and Medication
– Methoxyflourane
– Carbon tetrachloride
– Tetracycline
– Acetaminophen
– Elemental phosphorous
– Toluene
– Immunosuppressive
drugs
• Miscellaneous
– Amyloidosis
– Sarcoidosis
– Wilsons disease
– Hemochromatosis
– Venooclussive
disease
– Cryoglobulinemia
Key Point
• Hepatorenal syndrome does not include every
disease that affects the liver and kidney
simultaneously
• Hepatorenal syndrome is a distinct syndrome
that first requires the sequential initial
development of liver dysfunction accompanied by
portal hypertension and ascites culminating in
the development of acute kidney injury
Hepatorenal Syndrome :
“Non Essential” Diagnostic Criteria
• Additional supportive criteria but not
required for diagnosis
–Urine volume < 500 ml/day (65%)
–Urine sodium < 10 mEq/l
–Urine osm > plasma osm
–Serum sodium < 130 mEq/l
Clinical Types of Hepatorenal Syndrome
• Type I HRS
– Rapid deterioration in renal function
• < 2 weeks
– Doubling of initial SCr > 2.5 mg/dl
• Type II HRS
– Serum creatinine > 1.5 mg/dl
– Slow progressive course
Probability of Hepatorenal Syndrome
18
22
28
32
38
0
5
10
15
20
25
30
35
40
1 2 3 4 5
%
Years Followup
Gines A, et al. Gastroenterology 105:229-236,1993
N = 236 pts. nonazotemic + cirrhosis
Precipitating Factor – 50%
AKI Classification of Hepatorenal Syndrome
Hepatorenal Syndrome
ATN Pre renal Azotemia
Vasomotor Obstruction
Pre- Renal Azotemia
HRS-AKI Obstruction ATN
No
improvement
with Fluid
Urine Na low
FENA < 1%
No
Hydronephrosis
Portal HTN
Compression, Distortion,
Obliteration of Hepatic Architecture
Decreased Hepatic production
of vasodilatory substances
Activated Hypercontractile
Intrahepatic stellate cells
Intrahepatic Pressure and Early Portal HTN
Oliver J. Kidney Intern 77:669, 2010
Hepatofugal
NFPF (Non Forward Portal Flow) Blood flow
Away from the liver versus
Hepatopetal : normal flow into the liver
Backward Theory of Ascites Formation
Portal Hypertension / Hypoalbuminemia
Reversal of Starling’s Equilibrium in the Splanchnic Microcirculation
Increased Splanchnic Lymph Formation
Ascites Formation
Decreased Effective Circulatory Volume
Hepatorenal Syndrome
Backward Theory Hepatorenal Syndrome
Low urine sodium Yes Yes
Low blood pressure Yes Yes
Cardiac Output Decreased Increased
Systemic resistance Increased Decreased
Splanchnic Arterial Vasodilation
Increased vasodilatory substances
(nitric oxide)
Intestinal Bacterial translocation
Mesenteric Vascular
Hyporesponsivenss
Po
rtal
HT
N
Nitric Oxide in Cirrhosis
Liver Splanchnic
Decreased Increased
Gines P. N Engl J Med 361:1279, 2011
Role of bacterial
translocation through
permeable capillaries in the
intestines
Migration to lymph nodes with
increased cytokine release and
local inflammatory response
(PAMPs : pathogen-associated
molecular patterns)
Vasodilation
Increase in ascites
Hepatorenal Syndrome :
Mediators of Vasodilation-
Selective Splanchnic Vascular Hyporesponsiveness
• Glucagon
– Elevated levels in cirrhosis
• Desensitizes mesenteric circulation to
catecholamines and AII
• Direct vasodilation
• Increases cAMP leading to increased NO
synthesis
Blood Volume Distribution
Normal Cirrhosis
(Splanchnic pooling)
Blood Volume Distribution in Cirrhosis
27.324.7
29.7
37.711.412.8
2.3
5.2 18.2
25
0 5 10 15 20 25 30 35 40
Thorax
Abdomen
Liver
Spleen
Splanchnic
Normal Cirrhosis
% Blood Volume Distribution
Systemic Blood Flow and HRS
• Splanchnic arteriolar vasodilation IS NOT
accompanied by peripheral vasodilation in all
vascular beds
– Cerebral / Femoral / Brachial / Hepatic
beds all experience progressive
vasoconstriction which is directly related to
the GFR
Organ Perfusion in Cirrhosis and HRS
Splanchnic bed Cerebral blood flow
Renal blood flow
Coronary blood flow
Peripheral blood flow
Incr
ease
d
Dec
rea
sed
Total
Peripheral
vascular
resistance
DECREASES
RAAS Activation in Cirrhosis ± HRS
Progressive increase
in RAAS activation
with ascites
formation indicating
decreasing effective
circulating volume
In HRS there is
maximal RAAS
activation
Hepatorenal Syndrome : Pathophysiology
Splanchnic Arterial Vasodilation
Cirrhosis
Nitric Oxide
Glucagon
Endocannabinoids
Cytokines
Carbon Monoxide
Decreased Effective
Circulating Volume
Adaptive Response :
Increased Renal Vascular Resistance
Sodium and water Retention
Renin-Angiotensin-Aldosterone
Sympathetic Nervous System
Vasopressin / Increase water channels
Leukotriene E2
Endothelin-1
F2-isoprostanes
Counteradaptive
Response :
Intrarenal vasodilation
Natriuresis
Prostaglandins
Kallikreins
ANP
Hepatorenal Syndrome
Ring-Larsen H, et al. Scand J Clin Lab Invest 37:635-42,1977
Severe vasoconstriction of the cortical vessels in the kidney
in HRS which is completely reversible with therapy
Confirms that the injury is one of vascular tone
HRS
Transplanted
Doppler Ultrasound in HRS and Cirrhosis
Mindikoglu A. Clin Gastroenterology and Hepatology 2017
HRS
Cirrhosis
Normal
The resistive index is high throughout the renal vasculature in HRS to the
same degree – (no RI gap !)
In Cirrhosis alone the resistance is high in the larger vessels and not as
pronounced in the smaller vessels that have a lower resistive index (RI gap)
Precipitating Event
SBP, GI bleed, Large Volume Paracentesis
Splanchnic Vasodilation
Inadequate Cardiac Output
Increased AII, NE, ADH
Regional Vasoconstriction
Kidneys – HRS
Brain – Encephalopathy
Liver – Liver Failure
Adrenal – Adrenal Insufficiency
Increased Hepatic Resistance
Aggravation of Portal HTN
Circulatory Function and the Hepatorenal Syndrome
•Ruiz-del-Arbol L, et al. Hepatology 42:439,2005
Cardiac Output Renin Aldosterone
L/m
in
nl
nl
nl
Circulatory Function and the Hepatorenal Syndrome
Differences Between Type I and Type II HRS
6.2 5.8
4.6
0
1
2
3
4
5
6
7
No HRS Type II HRS Type I HRS
•Ruiz-del-Arbol L, et al. Hepatology 42:439,2005
CO
Hepato-Cardio-Renal Syndrome
• Cirrhotic Cardiomyopathy
– Clinical Features
• Blunted systolic and diastolic contractile
response to stress
• Ventricular hypertrophy / Dilation
• Prolonged Q-T interval
Cirrhosis
Increased Intrahepatic
Resistance
Increased Splanchnic
Vasodilators
Portal HTN
Splanchnic Vasodilation
Decreased Blood
Volume Distribution
Decreased Cardiac
Preload
Cirrhotic
Cardiomyopathy
Impaired
Contractility
+
Impaired
Relaxation
Impaired Effective
Circulating Volume
Activation of
Renal Vasoconstriction
Hepatorenal Syndrome
Type II HRS
HRS-CKD
Pathogenesis of Type I HRS (HRS-AKI)
Hepato – Cardio – Renal Syndrome
Peripheral Vasodilation Theory Peripheral Vasodilation +
Cardiomyopathy Theory +
acute decrease in volume
Arroyo V, J Hepatol 46:935, 2007
Risk for Developing Type I HRS
The “Second Hit “ Hypothesis
5
10
30
25
17
0
10
20
30
40
UGI Bleed Large Volume
Paracentesis
SBP Acute Alcoholic
Hepatitis
Hospital
admission for
Ascites
%
(> 5 L)
SBP risk : 30% in patients
with ascites
20% mortality rate
Circulatory Function and the Hepatorenal Syndrome
• Conclusions
– Patients who develop HRS have
• Lower baseline CO
• Higher baseline levels of renin / Aldosterone / Catecholamines
– Cardiac output decreases dramatically in Type I HRS resulting in a greater severity of renal hypoperfusion
• Etiology of “Cirrhotic cardiomyopathy”
– Chronic high catecholamine levels
• Left ventricular remodeling / fibrosis
• Diastolic dysfunction
Bile Cast Nephropathy
• Reported in patients with Direct bilirubin levels > 6 mg/dl and Total
bilirubin of 15 mg/dl
• Casts form primarily in the distal tubule but may be seen in the
proximal tubule
• Direct tubular toxicity secondary to mitochondrial dysfunction from
bile salts
• confirmed by two stains (Fouchet’s stain and Perl’s stain). Bile casts
were considered positive according to green color on Fouchet’s staining
(Halls stain) and negative Perl’s stain (Prussian blue)
AKI Classification of Hepatorenal Syndrome
Hepatorenal Syndrome
ATN Pre renal Azotemia
Vasomotor Obstruction
Pre- Renal Azotemia
HRS Obstruction ATN
No improvement with
Fluid but will improve
with albumin and
splanchnic
vasoconstriction
Direct tubular
toxicity of bilirubin
Intratubular
obstruction with casts
HRS is a combination of all 3 !
Pre Renal >>>>>>>>>>>> ATN >>>> Obstruction
Prevalence of HRS
as a Cause of AKI in Cirrhosis
%
Types of Kidney Disease seen in Cirrhosis
Prakash J. Renal Fail 33:40,2011
Kidney Diseases other than HRS
in Patients with Cirrhosis
• Hepatitis C
– Membranoproliferative glomerulonephritis
– Membranous GN
– Vasculitis
• Diabetes
– Diabetic Nephropathy
• Hepatitis B
– Membranous GN
– IgA nephropathy
– Vasculitis
In patients with AKI
and cirrhosis it is
essential to know the
cause of liver failure as
it may contribute to the
differential diagnosis
Do not forget !!!
Abdominal Compartment Syndrome
and Cirrhosis : AKI
Normal
Intra-abdominal pressure (IAP)
4 – 7 mmHG
Intra-abdominal hypertension (IAH)
12 – 20 mmHG
Intra-abdominal Compartment Syndrome (ICS)
12 – 20 mmHG
Abdominal Compartment Syndrome
and Cirrhosis : AKI
Increased Renal Venous HTN
Increased sub-capsular pressure
Decreased Renal Blood Flow
Decreased GFR
Hyponatremia in Cirrhosis and Ascites
Risk of Complications at 1 Month Followup
0
10
20
30
40
Encephalopathy HRS SBP GI Bleed
> 135 131 - 135 < 130
%
Angeli P. Hepatology 44:1535, 2006
Hepatorenal Syndrome :
Targets for Therapy
Reduce Splanchnic
Blood Flow
TIPS
Increase Splanchnic
Vasoconstriction
a-1 agonists
Midodrine
Noradrenaline
Glucagon antagonism
Somatostatin
Octreotide
V-1 agonists
Vasopressin
Terlipressin
Antagonize
Inflammation /
Bile Acids
Albumin infusion
Ursodeoxycholic acid
Albumin
• Non-Oncotic Properties
– Transport
– Free radical scavenging
• Sulfhydryl groups (thiols)
– Bind reactive oxygen species
• Superoxide hydroxyl
• Peroxynitrite
– Decreased Capillary permeability
– Decrease neutrophil adhesion and activation
– Anti-thrombotic and Anticoagulant effect
Hepatorenal Syndrome : Management Increase Splanchnic Vasoconstriction
• Terlipressin (non FDA approved )
– Vasopressin analogue
– Always combined with albumin infusion
– Bolus infusion
– Preferential vasoconstriction of the splanchnic vasculature (?)
• Increases blood pressure and renal perfusion pressure
• Decreases plasma renin, aldosterone, norepinephrine levels
• Increases ANP levels
Terlipressin in HRS :
Meta Analysis of Randomized Trials
• Sagi S. J of Gastroenterol Hepatol 25:880, 2010
Reversal of Type I HRS – 46%
Terlipressin in HRS :
Meta Analysis of Randomized Trials
• Sagi S. J of Gastroenterol Hepatol 25:880, 2010
7% serious
Ischemic
complications
Hepatorenal Syndrome :
Octreotide and Midodrine
• Therapy
– Target of treatment aimed at increasing mean arterial blood pressure by a minimum of 15 mmHg
• Midodrine (a-1 agonist)
– Oral administration
– 7.5 mg T.I.D. with maximum of 12.5 mg T.I.D.
• Octreotide (antagonist of glucagon)
– 100 mg T.I.D. subcutaneously with maximum 200 mg T.I.D.
– Albumin infused at 20 g/day and increased to a maximum of 40 g/day based on
• achieving a CVP > 12
Terlipressin vs Midodrine
Terlipressin Wins the Battle ! But ……..
Grey = Terlipressin
White = Midodrine + Octreotide
Grey = Partial response
White = Full response
Because Midodrine did not achieve a rise in BP the failure of
therapy may be related not to the drug combination but the lack of
titration to the proper blood pressure endpoint
Cavalin M.Hepatology Jan 16, 2015
Vasocontrictor Therapy in HRS
Change MAP
Responders 10 mmHg
Non-Responders 6 mmHg
Kiser T, et al. Neph Dial Transpl 20;1813, 2005
Increase in MAP > 10
Resulted in Improved Survival for HRS
MAP > 10
MAP < 10
Cai CX. Dig Dis Sci 2014 Dec 23
Noradrenaline Versus Terlipressin
in the Treatment of Type 1 Hepatorenal Syndrome
25 25
45
35
50
40
0
10
20
30
40
50
60
Day 4 Day 8 Day 15
Noradrenaline Terlipressin
%
Reversal
Praveen Sharma.Am J Gastroenterol. 2008 Jul;103(7):1689-97
Terlipressin vs Norepinephrine
It’s a Tie !!!
Nassar J.PLoS One. 2014 Sep 9;9(9):e107466
Israelsen M, Terlipressin versus other vasoactive drugs for
hepatorenal syndrome.Cochrane Database of Systematic Reviews
2017, Issue 9.
No benefit of
terlipressin
compared to
other
vasoconstrictors
Reversal of HRS Syndrome and
Lack of Improvement of Mortality
No improvement in mortality compared to other vasoconstricting therapy
Terlipressin and the FDA
• Approved in 40 countries for the treatment of HRS
–Not approved in Canada or the U.S. • U.S. Trials ongoing
– Mallinckrodt : Type 1 HRS currently in Phase 3 trials
– BioVie Inc : Ascites
• No current drugs have been approved for the
treatment of ascites
• Phase 2 Trials : Orphan Drug Designation
• Fast Track Application
HRS : Current Treatment Recommendations
• Administer one of the following vasoconsticting regimens
– Norepinephrine (0.5 – 3.0 mg/hr IV)
– Midodrine (7.5 – 12.5 mg p.o. T.I.D.) + Octreotide (100 – 200 mg SQ
T.I.D.)
– Terlipressin (0.5 – 2.0 mg IV q 4 – 12 hours)
• Concomitant administration of
– Albumin (1 g/kg IV on day 1 followed by 20 – 40 g/day )
• Duration of therapy – maximum 2 weeks
• Target increase in MAP by 10 mmHg
• CVP > 10 cmH2O
• Endpoint = reduction of creatinine < 1.5 mg/dl
Contraindications to Vasoconstrictor Use in HRS
• Active CAD
• Cardiomyopathy
• Cardiac Arrhythmias
• Cerebrovascular disease
• PVOD
• Severe HTN
Treatment of Refractory Ascites
Large Volume Paracentesis
Alfa Pump
Clonidine (0.1 mg in divided doses daily ) Midodrine 10 mg TID Large Volume Paracentesis (>5 L) + albumin 4-8 gm/L removed) Alfa Pump
No response to 400 mg/day Spironolactone . 160 mg /day of Furosemide
TIPS –Transjugular Portosystemic Shunt
Transjugular Intrahepatic Portosytemic Shunt
TIPS Placement
Reduces Portal Pressure
Prevention of HRS by Placement of TIPS
Castells A, Hepatology. 1994;20(3):584
%
Alfa Pump for Refractory Ascites
(Automated Low-Flow Ascites Pump)
Bureau C. Journal of Hepatology 2017 vol. 67 j 940–949
fully implantable, programmable, and rechargeable pump system that
automatically diverts ascitic fluid from the peritoneal cavity to the urinary
bladder, allowing fluid removal by micturition
Mean duration of implant procedure was 65.0 ± 20.6 min (min. 30, max. 130), all
were performed under general anesthesia (12 laparoscopically [44.4%], 15 open
[55.6%]).
Efficacy currently limited by risk of infection
Liver Transplantation in HRS
Liver TP Alone Liver / Kidney TP
?
HRS Diagnosis
• From a Nephrologic Perspective
– Prolonged ischemic and vasoconstriction will lead to
upregulation of cytokines that lead to progressive
sclerosis
– The duration of time required for these irreversible
events is not measurable or defined
Hepatic Glomerulosclerosis Mesangial contraction Decreased renal blood flow
MELD Score
• Point criteria for determining the allocation of
liver TP
• MELD = Medical Evaluation of Liver Disease
– Major factors
• INR
• Bilirubin
• Creatinine
Marked Increase in the Number of
Simultaneous Liver/Kidney Transplants since
the Inception of the MELD Score
What We Want to Avoid !
Risk of CKD is Dependent on Pre-TP Renal
Function in Non-Renal TP Patients
0
0.5
1
1.5
2
2.5
3
3.5
4
> 90 60 - 89 30 - 59 < 29
Liver TP Heart TP Lung TP
OR
GFR
It is absolutely essential to
maximize the GFR in liver TP
candidates to minimize the
risk of post- TP CKD
Transplantation in HRS :
Liver or Combined Liver-Kidney • Key concepts
– HRS is not an indication for combined liver –kidney transplant
• HRS will recover in 80% of patients posttransplant
– Kidney TP should be given only to patients with
• ESRD : Dialysis > 3 months
• CKD (3 months) with a GFR < 30 cc/min
– These patients will likely require dialysis within 3 years after
transplantation with CNI exposure
• AKI
– Dialysis > 6 weeks
– GFR < 25 cc/min > 6 weeks
– Pre-transplant renal function directly affects liver TP survival
• All efforts to treat HRS and improve renal function before
transplantation are important
Hepatorenal Syndrome : Transplantation
One or Two Organs ?
• By definition –
– Hepatorenal syndrome is a reversible phenomena of
functional nature rather than structural damage
– Patients meeting the strict criteria for this syndrome should
be transplanted with a liver TP only
– Kidney TP if Stage 4 CKD or dialysis dependent for > 6
weeks
• Management concern
– Risk of calcineurin nephrotoxicity in a kidney that has been
under prolonged ischemia
– Difficulty of obtaining a renal biopsy due to the
coagulopathy of liver failure
Hepato(cardio)renal Syndrome
• A unique constellation of hemodynamic events
associated with advanced liver failure resulting in a
form of vasomotor nephropathy
– Must be distinguished from ATN, pre-renal azotemia
and coincident involvement of the kidneys and the
liver by specific disease states
• Primary splanchnic arteriolar vasodilation appears to be
the main pathogenesis
Hepatorenal Syndrome
• HRS rarely develops spontaneously but often
accompanies acute iatrogenic changes in
intravascular volume
• Treatment with TIPS, Octreotide + Midodrine,
Noradrenaline, Vasopressin analogues (with albumin-
when approved!) and/or liver transplantation has
been successfully employed in HRS
• HRS has a major adverse long term impact on patient
survival and precautions must be initiated to avoid
this syndrome
Thank you !
Miami Transplant Institute #1 in the U.S.
University of Miami #1
2017 Transplant Program
in the U.S.
Volume / Outcomes